Liquid biopsy profiling of PARPi-resistance breast cancer patients indicates that many patients develop multiple reversion mutations, and that alterations in the 53BP1-Shieldin pathway are present but less frequent. The co-occurrence of 53BP1-Shieldin pathway mutations and reversion mutations suggests parallel mechanisms of resistance can operate in the same patient.

over 1 year ago

Liquid biopsy • BRCA Biomarker • PARP Biomarker • Biopsy

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • TP53BP1 (Tumor Protein P53 Binding Protein 1)

BRCA2 mutation • BRCA1 mutation • BRCA2 deletion • BRCA1 deletion • BRCA1 rearrangement

2years

BRAVO: A Phase III Trial of Niraparib Versus Physician's Choice in HER2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients (clinicaltrials.gov)

P3, N=216, Terminated, Tesaro, Inc. | Completed --> Terminated; The study was terminated due to futility.

2 years ago

Trial termination

HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)

BRCA2 mutation • BRCA1 mutation • EGFR mutation • HR positive • HER-2 negative • BRCA mutation • BRCA1 positive • BRCA1 rearrangement • BRCA2 positive

Zejula (niraparib)

2years

large genome rearrangement of BRCA1/2 in BRCA mutation negative ovarian cancer patients (AACR-NCI-EORTC 2022)

The detection of more BRCA1/2 mutations in patients of ovarian cancer is important for efforts to provide targeted therapy. No

2 years ago

Clinical • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)

BRCA2 mutation • BRCA1 mutation • BRCA mutation • BRCA2 rearrangement • BRCA1 negative • BRCA1 rearrangement

over3years

5' Region Large Genomic Rearrangements in the BRCA1 Gene in French Families: Identification of a Tandem Triplication and Nine Distinct Deletions with Five Recurrent Breakpoints. (PubMed, Cancers (Basel))

Taken together, our results firmly establish that the BRCA1 5' region is a frequent site of different LGRs and highlight the importance of the segmental duplication and Alu sequences, particularly the very high homologous region, in the mechanism of a recombination event. This also confirmed that those events are not systematically deleterious.

over 3 years ago

Journal

BRCA1 (Breast cancer 1, early onset)

BRCA1 rearrangement

over3years

A novel BRCA1 duplication and new insights on the spectrum and frequency of germline large genomic rearrangements in BRCA1/BRCA2. (PubMed, Mol Biol Rep)

Our data demonstrate that BRCA1-2 LGRs should be considered when ordering genetic testing for individuals with a personal or family history of cancer, particularly breast cancer. Further research could shed light on BRCA1-2 LGRs' unique carcinogenesis roles.

over 3 years ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)

BRCA2 mutation • BRCA1 mutation • BRCA2 deletion • BRCA1 deletion • BRCA1 rearrangement

over3years

Local Laboratory Testing of Germline BRCA Mutations vs. Myriad: A Single-Institution Experience in Korea. (PubMed, Diagnostics (Basel))

All discrepancies were generated during interpretation of BRCA 2 gene sequencing. Further studies and standardization of genetic testing for BRCA 1/2 genes are required.

over 3 years ago

Clinical • Journal • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)

BRCA2 mutation • BRCA1 mutation • HER-2 negative • BRCA mutation • BRCA1 rearrangement